We have demonstrated high levels of human immunodeficiency virus (HIV) DNA and RNA synthesis in peripheral blood mononuclear cells during primary HIV infection. Dramatic downregulation of the levels of HIV RNA synthesis coincides with the emergence of HIV-specific immune responses. There is a discrepancy, however, between the downregulation of viremia and the minimal or lack of detection of changes in the levels of HIV DNA in mononuclear cells. In the simian immunodeficiency virus (SIV) model numerous individual infected cells were localized in peripheral lymph nodes of monkeys as early as day 7 post-inoculation. Trapping of virions in the follicular dendritic cell (FDC) network was initially detected at week 2 post-inoculation and progressively increased over time, whereas the number of SIV-infected cells decreased. Trapping of virions in the FDC network was temporally associated with a rise in the levels of complement-binding antibodies. Similar kinetics of HIV distribution in lymph nodes have been observed in individuals with primary HIV infection. We have demonstrated major expansions in T cells manifesting a restricted set of Vbeta families during the primary immune response to HIV. Cells expressing the expanded Vbetas were predominantly CD8+ T lymphocytes, and were activated. These expanded CD8+ T-cell subsets were involved in the expression of cytokines, and mediated specific cytotoxic activity againt HIV envelope was detected within the expanded cell populations. Nucleotide sequences of recombinant clones of the expanded Vbetas demonstrated the oligoclonal (i.e., antigen-specific) nature of these expansions. We have demonstrated that the expansion of these Vbeta families was driven by HIV antigens. Three patterns of Vbeta expansions were observed. These different patterns appear to be associated with different clinical outcomes.